Taylorellegaard9704
High throughput in vivo laboratory models is need for screening and identification of effective therapeutic agents to overcome microbial drug-resistance. This study was undertaken to evaluate in vivo antimicrobial efficacy of short-chain antimicrobial peptide- Cecropin A (1-7)-Melittin (CAMA) against three multi-drug resistant enteroaggregative Escherichia coli (MDR-EAEC) field isolates in a Galleria mellonella larval model. The minimum inhibitory concentration (MIC; 2.0 mg/L) and minimum bactericidal concentration (MBC; 4.0 mg/L) of CAMA were determined by microdilution assay. CAMA was found to be stable at high temperatures, physiological concentration of cationic salts and proteases; safe with sheep erythrocytes, secondary cell lines and commensal lactobacilli at lower MICs; and exhibited membrane permeabilization. In vitro time-kill assay revealed concentration- and time-dependent clearance of MDR-EAEC in CAMA-treated groups at 30 min. CAMA- treated G. mellonella larvae exhibited an increased survival rate, reduced MDR-EAEC counts, immunomodulatory effect and proved non-toxic which concurred with histopathological findings. CAMA exhibited either an equal or better efficacy than the tested antibiotic control, meropenem. This study highlights the possibility of G. mellonella larvae as an excellent in vivo model for investigating the host-pathogen interaction, including the efficacy of antimicrobials against MDR-EAEC strains.Bisphenol S (BPS) has been detected in personal care products, water, food and indoor house dust, demonstrating the potential for human exposure. Due to limited data to characterize the hazard of BPS, the National Toxicology Program (NTP) is investigating the toxicity of BPS in rodent models. Generating systemic exposure data is integral to putting toxicological findings into context. The objective of this work was to develop and validate a method to quantitate free (unconjugated parent) and total (free and all conjugated forms of) BPS in rodent plasma, amniotic fluid and fetal homogenate in support of NTP studies. The method used incubation with (total BPS) and without (free BPS) deconjugating enzyme and then protein precipitation followed by ultra-performance liquid chromatography-tandem mass spectrometry. In Sprague Dawley rat plasma, the method was linear (r ≥ 0.99) over the range 5-1,000 ng/mL, accurate (mean relative error (RE) ≤ ±10.5%) and precise (relative standard deviation (RSD) ≤ 7.7%). Mean recovs to BPS.Micromanipulators, more than any other instrument, opened the early doors to developing the powerful genetics of yeast that underlies much of the molecular work today. The ability to separate the spores of a tetrad and analyze their phenotypes generated the genetic maps and biology upon which subsequent cloning, sequencing, cutting edge molecular and cell biology depended. This work describes the development of those micromanipulators from garage to barn to factory and the developer of the sophisticated instruments we use today. For more than 30 years Carl Singer and his family were staunch and generous supporters of the International Conferences on Yeast Genetics and Molecular Biology meetings both in Europe and America. Carl Singer's displays at meetings became a traditional fixture and engaged the appetites of many students and advanced researchers to employ a technique that many perceived as too complicated or difficult, but which he made simple and easy to learn. His experiences also document a sketch of the international yeast meetings, their venues and how they developed through the years.The human gut microbiota respond to particular food components, interact with intestinal mucosa and thereby contribute to health and diseases. Key microbiome features are under comprehensive investigation and are likely to be developed as reliable evidences for clinical diagnosis. And the underlying mechanisms lay the foundation of assembling bespoke nutritional ingredients including functional food additives that may lead to favorable outcomes in facilitating amelioration of host dysfunctions. Functional hydrocolloids serve as multiple food additives with promising application prospects and outstanding adjunctive beneficial characteristics. Therefore, in this review, we introduce the latest advances in food additives-gut microbiota-host axis by summarizing the physiochemical and physiological properties of a collection of functional hydrocolloids from various sources, describing the functional hydrocolloids-related intestinal commensal markers, and deciphering the underlying mechanisms of their beneficial effects, and propose the feasibilities and guidelines for further developments of gut microbiota-oriented personalized nutrition.The article examines key developments unfolding in the 21st century in the intersection of multisectoral and multilateral dimensions of public health policy. Several processes and mechanisms, relatively new or rapidly evolving, are fuelling this dynamic interface. They include, in particular, expansion of the spectrum of sectors involved in the health domain, the upsurge of trans-border and commercial determinants of health, growing presence of health issues in multilateral instruments and processes that are outside of the health sector, and strengthening the legal base of intersectoral relations and responsibilities for health. They also encompass and reflect important transformations in health diplomacy and governance for health, some of the fundamentals of contemporary public and global health. The article argues that overall, multisectoral and multilateral dimensions tend to interact, inform and reinforce each other, and that such interaction would be one of important drivers of 21st century intersectoral policy-and international cooperation-for health.
In Japan, while it is known that underweight women over the age of 40 years have a high risk for type 2 diabetes, there is a lack of clarity on the association between glucose tolerance and underweight in younger women. Accordingly, we investigate the prevalence and features of impaired glucose tolerance (IGT) in young underweight Japanese women.
In this cross-sectional study, we recruited 56 normal weight and 98 underweight young Japanese women and evaluated their glucose tolerance levels using an oral glucose tolerance test. Then, we compared the clinical characteristics associated with normal glucose tolerance (NGT) and IGT in the underweight women. Insulin secretion, whole-body insulin sensitivity, and adipose tissue insulin resistance values were measured using the insulinogenic index, whole-body insulin sensitivity index (Matsuda index), and adipose insulin resistance index (Adipo-IR), respectively. Fitness level (peak VO2) was measured using an ergometer.
The prevalence of IGT was higher in the underweight women than the normal weight women (13.3% vs 1.8%). The underweight women with IGT showed a lower insulinogenic index, lower peak VO2, and Matsuda index and a higher fasting free fatty acid level and Adipo-IR than those with NGT. The whole-body composition was comparable between the NGT and IGT groups.
The prevalence of IGT was higher in young Japanese women with underweight than those with a normal weight. The underweight women with IGT showed impaired early-phase insulin secretion, low fitness levels, and reduced whole-body and adipose tissue insulin sensitivity levels.
The prevalence of IGT was higher in young Japanese women with underweight than those with a normal weight. The underweight women with IGT showed impaired early-phase insulin secretion, low fitness levels, and reduced whole-body and adipose tissue insulin sensitivity levels.The novel coronavirus (SARS-CoV-2) has become a pandemic and is threatening human health globally. Here, we report nine newly evolved SARS-CoV-2 single nucleotide polymorphism (SNP) alleles those underwent a rapid increase (seven cases) or decrease (two cases) in their frequency for 30-80% in the initial four months, which are further confirmed by intrahost single nucleotide variation analysis using raw sequence data including 8,217 samples. The nine SNPs are mostly (8/9) located in the coding region and are mainly (6/9) nonsynonymous substitutions. The nine SNPs show a complete linkage in SNP pairs and belong to three different linkage groups, named LG_1 to LG_3. Analyses in population genetics show signatures of adaptive selection toward the mutants in LG_1, but no signal of selection for LG_2. Firsocostat cost Population genetic analysis results on LG_3 show geological differentiation. Analyses on geographic COVID-19 cases and published clinical data provide evidence that the mutants in LG_1 and LG_3 benefit virus replication and those in LG_1 have a positive correlation with the disease severity in COVID-19-infected patients. The mutants in LG_2 show a bias toward mildness of the disease based on available public clinical data. Our findings may be instructive for epidemiological surveys and disease control of COVID-19 in the future.
Sjögren's syndrome is an autoimmune disease most commonly diagnosed in adults but can occur in children. Our objective was to assess the presence of chemokines, cytokines, and biomarkers (CCBMs) in saliva from these children that were associated with lymphocyte and mononuclear cell functions.
Saliva was collected from 11 children diagnosed with Sjögren's syndrome prior to age 18 years and 16 normal healthy children. 105 CCBMs were detected in multiplex microparticle-based immunoassays. ANOVA and t test (0.05 level) were used to detect differences. Ingenuity Pathway Analysis (IPA) was used to assess whether elevated CCBMs were in annotations associated with immune system diseases and select leukocyte activities and functions. Machine learning methods were used to evaluate the predictive power of these CCBMs for Sjögren's syndrome and were measured by receiver operating characteristic (ROC) curve and area under curve (AUC).
40.9% (43/105) CCBMs were different (p < 0.05) in children with Sjögren's syndrome compared to the healthy study controls and could differentiate the two groups (p < 0.05). Elevated CCBMs in IPA annotations were associated with autoimmune diseases and with leukocyte chemotaxis, migration, proliferation, and regulation of T-cell activation. The best AUC value in ROC analysis was 0.93, indicating that there are small numbers of CCBMs that may be useful for diagnosis of Sjögren's syndrome.
While 35/43 CCBMs have been previously reported in Sjögren's syndrome, 8 CCBMs had not. Additional studies focusing on these CCBMs may provide further insight into disease pathogenesis and may contribute to diagnosis of Sjögren's syndrome in children.
While 35/43 CCBMs have been previously reported in Sjögren's syndrome, 8 CCBMs had not. Additional studies focusing on these CCBMs may provide further insight into disease pathogenesis and may contribute to diagnosis of Sjögren's syndrome in children.Sexual dimorphism in gene expression is likely to be the underlying source of dimorphism in a variety of traits. Many analyses implicitly make the assumption that dimorphism only evolves when selection favors different phenotypes in the two sexes, although theory makes clear that it can also evolve as an indirect response to other kinds of selection. Furthermore, previous analyses consider the evolution of a single transcript or trait at a time, ignoring the genetic covariance with other transcripts and traits. We first show which aspects of the genetic-variance-covariance matrix, G, affect dimorphism when these assumptions about selection are relaxed. We then reanalyze gene expression data from Drosophila melanogaster with these predictions in mind. Dimorphism of gene expression for individual transcripts shows the signature of both direct selection for dimorphism and indirect responses to selection. To account for the effect of measurement error on evolutionary predictions, we estimated a G matrix for eight linear combinations of expression traits.